The present invention relates to the treatment of gastric dyspepsia by oral administration of rifaximin.
Two Australian microbiologists, Warren J. R. and Marshall B., reported in Lancet, 1983, 1, 1273-1275, that they had identified in gastric biopsies from patients affected with gastric dyspepsia some curved and storiform bacilli which were initially erroneously believed to belong to the Campylobacter species. Later, Goodwin C. S. et al, Int. J. Syst. Bact. 39, 397-405, 1989, made a more precise classification of the micro-organism, which had no elements in common with the Campylobacter genus, and used the name of Helicobacter pylori, derived from the helical form of the bacterium and from its preferred location in the pylorus. Marshall B. et al., Med. J. Australia, 142, 436-439, 1985 and Morris A., Nicholson G., Am.J. Gastroenterol., 82, 192-199, 1987, demonstrated the pathogenic nature of this bacterium which causes gastritis in man.
McNulty C. A. M. et al., Antimicrob. Agents Chemother., 28, (6), 837-838, 1985 and Shungu D. L. et al., Antimicrob. Agents Chemother., 31, (6) 949-950, 1987, have demonstrated the in vitro activity of several antibiotics against this bacterium. In particular, they demonstrated the vigorous antibacterial in vitro activity of antibiotics containing a beta-bactam group, penicillin, ampicillin, cefoxttin and imipenem, quinolones: norfloxacin and cyprofloxacin, aminoglycosides: gentamicin and erythromycin, and also tetracycline and metronidazole and the lack of in vitro activity of other antibacterial agents like sulfa drugs, trimethoprim, nalidixic acid.
It has been found, however, that the proved antibacterial activity in vitro does not automatically give the antibacterial agents a therapeutic activity in vivo on Helicobacter pylori. Mertens J. C. C. et al, Antimicrob. Agents Chemother., 33, 2, 256-257, 1989, demonstrated that norfloxacin, a powerful quinolone antibiotic, active in vitro against the bacteria with M.I.C. 90% equal to 1 .mu.g/ml, is unable to eradicate Helicobacter pylori in 15 out of 17 patients after a month of treatment.
This therapeutic failure, sharply contrasting with the proved in vitro activity of norfloxacin against Helicobacter pylori, is attributed both to the bacterial resistance, acquired in as many as 9 cases during the antibiotic treatment, and to the fact that the antibiotic does not penetrate sufficiently into the deeper layers of the gastric mucous harbouring the bacteria. The lack of antibacterial action in vivo was further demonstrated by histological data and by the symptoms which remained unaltered.